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Session: Nutrients and Inflammation (Oral 10)

(OR10-04-23) Comparative Study of Tart Cherry and Fructooligosaccharides Reveals Alterations in the Gut-Bone Axis Independent of T Regulatory Cells in Young Adult C57BL/6 Female Mice

Sunday, July 23, 2023
2:36 PM – 2:48 PM ET
Location:  Constitution B
Disclosure(s):
Brenda J. Smith, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Sanmi A. Alake, MS: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: The gut-bone axis represents a promising target for osteoporosis prevention, but the mechanisms remain unclear. Recently, short chain fatty acid (SCFA)-induced changes in T regulatory cells [Tregs] were reported to mediate the benefits on bone. This study investigated how two prebiotics, tart cherry (TC) and fructooligosaccharide (FOS), affect bone and whether Tregs are required for the response.

Methods: Eight-week-old C57BL/6 female mice (n=96) were randomized to six groups in a 2x3 design, antibody (anti-CD25 or isotype control) and diets (AIN-93M control, 10%TC, or 10%FOS). After 8 wks, bone structural parameters, gut and bone Tregs, fecal SCFAs, regulators of bone cell differentiation and activity, chemokines and cytokines were assessed. Data were analyzed using 2-way ANOVA, followed by post-hoc tests.

Results: Anti-CD25 suppressed (P < 0.01) ileal and bone marrow CD4+CD25+FOXP3+ Tregs by >96%. Irrespective of CD25, FOS increased bone mineral content (P < 0.01), density (P < 0.05), trabecular bone volume (P < 0.01) in the vertebra (40%) and tibia (30%) compared to control and TC groups. Only FOS increased Tregs (P < 0.01) in the ileum. TC and FOS increased (P < 0.01) fecal SCFAs, but the FOS effect was greater than TC. In bone, only FOS increased (P < 0.01) the expression of genes that regulate osteoblast differentiation and activity (bone morphogenetic protein 2 [Bmp2], Osterix, type 1 collagen [Col1α1]. Both FOS and TC increased genes expressed by osteocytes (P < 0.01), phosphate regulating endopeptidase x-linked (Phex) and matrix extracellular phosphoglycoprotein (Mepe); however, only FOS increased sclerostin (SOST) (P < 0.01) and dentin matrix acidic phosphoprotein 1 (Dmp-1) (P < 0.01) compared to controls. These transcriptional changes occurred regardless of CD25. No regulators of osteoclasts were altered. FOS decreased ileal chemokines (P < 0.01) involved in T cell trafficking (C-X-C chemokine receptor type 4 [CXCR4] & CXC ligand 12 [CXCL12]) (P < 0.01), and proinflammatory cytokines (P < 0.05) (interleukin, IL-17 & IL-23) compared to controls. TC did not affect these cytokines and chemokines.

Conclusions: These findings demonstrate that FOS promotes bone health to a greater extent than TC in young adult mice and activates osteoblasts and osteocytes, independent of Tregs.

Funding Sources: NIH